tbuckley/cabot-search huggingface dataset:
Molecular testing and patterns of treatment in patients with NSCLC: An IASLC analysis of ASCO CancerLinQ Discovery Data.
Authors: Madhusmita Behera, Gregory Joseph, Manali Rupji, Zhonglu Huang, Becky Bunn, Murry Wynes, Jeffrey M. Switchenko, Giorgio V. Scagliotti, Kristin Ann Higgins, Ming Sound Tsao, Chandra Prakash Belani, Lecia V. Sequist, Suresh S. Ramalingam
Journal: Journal of Clinical Oncology (2022)

9128 Background: Precision medicine has resulted in improved outcomes for non-small cell lung cancer (NSCLC); while molecular testing is considered critical for guiding treatment decisions for advanced stage NSCLC, adoption of testing in routine practice is variable. We analyzed the factors contributing to molecular testing and treatment patterns in patients with lung cancer. Methods: The ASCO CancerLinQ Discovery dataset was queried to identify patients diagnosed with lung cancer between the years 2010-2018. Data on demographics, tumor stage, histology and treatments were extracted, and receipt of molecular testing was investigated as the primary outcome. Univariate association of each clinicopathological variable with molecular testing outcome was performed using chi-square test for categorical variables and ANOVA test for numerical variables. A multivariable logistic regression analysis with backward selection at an alpha of 0.05 was reported. All analyses were conducted using SAS 9.4. Results: A total of 37,925 NSCLC patients with stage IV disease were analyzed. Patient characteristics: median age 65 years, 51% male, 68% white, 33.5% adenocarcinoma. Approximately 22% of all NSCLC patients had molecular testing results. In adenocarcinoma patients, 49% had molecular testing results available. In the stage IV group, 47% were treated with chemotherapy, 16% with immunotherapy and 3% with targeted therapy. On multivariable analysis, females were more likely to have molecular testing compared to males [(OR: 1.29 (1.22-1.37); p &lt; 0.001]. Compared to White patients, Black patients were less likely to have molecular testing [OR: 0.89 (0.81-0.97); p = 0.009] and Asians were more likely to undergo testing [OR: 2.22 (1.79-2.75); p &lt; 0.001]. Hispanic patients were more likely to undergo molecular testing compared to non-Hispanics [OR:1.24 (1.02-1.52); p = 0.03]. Additionally, treatment with immunotherapy [OR: 1.86 (1.72-2.01); p &lt; 0.001] and targeted therapy [OR: 2.29 (2.00-2.64); p &lt; 0.001] were associated with significantly higher likelihood of having molecular testing. These results were also confirmed on a subgroup analysis of adenocarcinoma patients. Conclusions: In this analysis of a US-based real-world dataset of stage IV NSCLC patients, White race and female sex are associated with higher likelihood of having molecular test performed. The percentage of patients undergoing testing remains sub-optimal.
Clinical outcomes of patients with metastatic Hormone-Sensitive Prostate Cancer (mHSPC) with Prostate-Specific Antigen (PSA) decline to undetectable levels on enzalutamide (ENZA): Post hoc analysis of ARCHES
Authors: A. Stenzl, N.D. Shore, A. Villers, T. Iguchi, F. Gomez-Veiga, A. Alcaraz, B. Alekseev, AA. Azad, RZ. Szmulewitz, D. Petrylak, J. Holzbeierlein, B. Rosbrook, F. Zohren, G.P. Haas, G. Gourgioti, N.N. El-Chaar, A.J. Armstrong
Journal: European Urology (2022)
Factors associated with altmetric attention scores for randomized phase III cancer clinical trials.
Authors: Michael Kevin Rooney, Ethan B. Ludmir, Clifton Dave Fuller, Jeremy Lyle Warner
Journal: Journal of Clinical Oncology (2022)

11014 Background: The rise of the internet and social media has created new opportunities for the rapid sharing of scientific findings among professional and public communities. Altmetric Attention Scores (Altmetrics) are real-time measures of scientific impact and attention through various public outlets, including news, blogs, and social media. Distributions and patterns of Almetrics for high-impact clinical cancer research remain under-reported. Our goal was to describe the relationship between Altmetrics and other characteristics of published trials. Methods: We identified all two-arm superiority phase III cancer randomized controlled trials (RCTs) with a publication date between 2015-2020 from HemOnc.org. For included trials, we tabulated the followed the data: Altmetric score as of February 11, 2022; positive study (yes/no); FDA registration trial (yes/no); primary endpoint (categorized as overall survival (OS), progression-free survival (PFS), event-free/disease-free survival (EFS/DFS), or other); journal tier (defined as tier 1: NEJM, Lancet, JAMA; tier 2: JCO, Blood, Lancet Oncology, JAMA Oncology, Annals of Oncology or Tier 3: other). Univariable testing was performed with Pearson correlation, Wilcoxon rank sum, and Kruskal-Wallis testing to identify associations between predictor variables and Altmetrics. For factors with significant univariable associations, we generated a multiple linear regression model to identify clinical trial factors predictive of Altmetric attention scores, with alpha = 0.05 defining statistical significance. Results: Of 673 publications identified per inclusion/exclusion criteria, Altmetric scores were found for 638 (95%). The median score was 38.9 (IQR 12.4-126.7) – well above the 95 th percentile for all Altmetric scores. On univariable testing, positive studies (P &lt; 0.001), registration trials (P &lt; 0.001), those published in tier 1 journals (P &lt; 0.001), and trials with primary endpoint of OS (P = 0.002) were associated with increased Altmetric scores. On multivariable testing, positive studies (P = 0.006), registration trials (P &lt; 0.001), studies published tier 1 journals (P &lt; 0.001), and those reporting on OS (P = 0.03) persisted as significantly associated with increased engagement as measured by Altmetric scores. Conclusions: Social media and other online platforms represent an increasingly important avenue for the sharing of scientific and medical research. In this cross-sectional observational study, we found that certain characteristics of cancer clinical trials and publications are predictive of impact as measured by Altmetric scores. Specifically, positive registration trials published in traditionally defined high-impact journals and those reporting on OS as a primary endpoint tend to have the greatest Altmetric attention scores. The significance and consequences of these relationships warrant further investigation.
Improvements in life expectancy among childhood cancer survivors: Uneven gains and remaining challenges.
Authors: Jennifer M Yeh, Zachary J. Ward, Kayla Stratton, Gregory T. Armstrong, Eric Jessen Chow, Melissa M. Hudson, Lindsay M. Morton, Kevin C. Oeffinger, Lisa Diller, Wendy M. Leisenring
Journal: Journal of Clinical Oncology (2022)

10050 Background: Childhood cancer survivors are at risk for shortened lifespan. Projections of life expectancy (LE) by diagnosis can provide benchmarks for assessing improvements over time. Methods: We developed a simulation model to project risk for common, life-threatening chronic health conditions (CHCs; heart failure, myocardial infarction, valvular disease, stroke, secondary breast cancer, colorectal cancer, glial tumors, sarcomas) and excess mortality among 5-year survivors, based on patient characteristics (sex, age at diagnosis, diagnosis) and treatment exposures (chemotherapy, radiation dose). Risk was estimated using statistical models and Childhood Cancer Survivor Study data. Age-related CHC risks (SEER, NHLBI) and competing mortality (CDC Wonder) were based on national databases. We used model calibration to identify parameter sets that generated outcomes consistent with observed data. Model outcomes included conditional LE and 10-year survival probability at age 40. For comparisons to the general population, we simulated age-, sex-, and diagnosis year-matched individuals who faced only competing mortality rates. Results: Among a cohort representative of the CCSS (mean diagnosis age, 7.4 yrs), compared to the general population, the gap in LE among survivors diagnosed in the 1970s vs. 1990s decreased from 17 yrs (25%) to 11 yrs (17%). Changes in LE among survivors diagnosed in the 1990s vs. 1970s varied by diagnosis, with leukemia, lymphoma, and CNS tumor survivors estimated to live an additional 8 to 11 yrs (Table). In contrast, considerably smaller gains were estimated for sarcoma and renal tumor survivors (1–3 yrs) and a loss for neuroblastoma (-3 yrs). Among survivors who reached age 40, the probability of surviving an additional 10 years increased from 89% to 92% between 1970s vs. 1990s, with the greatest gains for lymphoma and CNS tumors. Conclusions: Although temporal changes in pediatric oncology are projected to result in LE gains among survivors, considerable variation is projected across diagnoses. These findings highlight the uneven success of improving treatments for all cancers. [Table: see text]
Role of metformin in the treatment of cholangiocarcinoma: A systematic review.
Authors: Aisha Olanike Adigun, Aleena Naeem, Keerthi Poladi, Vivek Soorya Sathya Moorthy, Farwah Fatima, Muhammad Ahmad, Zarlakhta Zamani, Mobeen Zaka Haider, Nilofar Zamani, Muhammad Umair Mushtaq
Journal: Journal of Clinical Oncology (2022)

e16132 Background: Non-cancer medications and their potential anti-cancer activity have attracted significant interest in recent years. The aim of this research is to conduct a systematic assessment of the existing evidence on the usefulness of metformin in the treatment of cholangiocarcinoma. Methods: We conducted literature search using PubMed, Clinicaltrials.gov, Embase, and Cochrane to retrieve studies evaluating the role of Metformin in the treatment of Cholangiocarcinoma. Three studies were finalized after careful screening. Results: We analyzed 3 studies. The total population was 638. The types of Cholangiocarcinoma varied from intrahepatic cholangiocarcinoma found in 293, to extrahepatic Cholangiocarcinoma in 365 and gallbladder carcinoma in 149 patients. Patients were in different stages of treatment such as undergoing chemotherapy, surgery or post- resection and/or post chemotherapy. The mean survival rate was significantly increased to 30.4 months and 13.2 months in patients using Metformin vs. 23.48 months and 10.3 months among patients not using Metformin (p &lt; 0.0005) after resection of the tumor. An increase in the mean survival rate was reported among patients using Metformin vs. non-users after the administration of chemotherapy, i.e., 25.9 months vs. 10.6 months (p = 0.0016), respectively. Metformin in combination with Chloroquine showed favorable results regarding adverse events, however, no clinical activity was reported against IDH-1 mutated intrahepatic cholangiocarcinoma. Conclusions: Our analysis concludes while the use of Metformin is associated with significantly improved post-operative survival, it does not show any significant clinical activity against IDH-1 mutated intrahepatic cholangiocarcinoma. Metformin also showed significant improvement in patients taking chemotherapy. Studies, including trials to evaluate the effectiveness of Metformin alone or used in combination with non-cancer medications or chemotherapeutic agents could provide more definitive recommendations for the treatment of Cholangiocarcinoma.[Table: see text]
In the era of computed tomography volumetry: Is isotope renography still routinely required in the preparation and selection of living kidney donors?
Authors: B. Ali-El-Dein, A. Galal, M.H. Zahran, H. Refaie, M.E. Mashaly, M.T. Fouad, A.F. Refaie, I. Saeed, M. Atteya, Y. Osman
Journal: European Urology (2022)
Pembrolizumab outperforms tyrosine kinase inhibitors in the adjuvant therapy of patients with high-risk renal cell carcinoma: A systematic review and network meta-analysis
Authors: E. Laukhtina, F. Quhal, K. Mori, R. Sari Motlagh, S. Katayama, P. Rajwa, T. Yanagisawa, N.С. Grossmann, H. Mostafaei, F. König, A. Aydh, B. Pradere, J.Y. Teoh, D. Enikeev, P.I. Karakiewicz, M. Schmidinger, S.F. Shariat
Journal: European Urology (2022)
Prognostic role of tumor stroma ratio, tumor-infiltrating lymphocytes, and tumor budding in patients with intestinal-type gastric cancer after radical resection.
Authors: Dan Sha, Chunfang Tian, Frank A. Sinicrope, Haiyan Jing, Jinshen Wang, Wei Song
Journal: Journal of Clinical Oncology (2022)

4055 Background: Tumor microenvironmental (TME) features including tumor stroma ratio (TSR), tumor infiltrating lymphocytes (TILs) and tumor budding (TB), may be associated with tumor metastatic potential. We sought to identify the association of these features with prognosis of patients with resectable intestinal-type gastric cancer. Methods: Radical resection of gastric carcinoma (&gt; 15 LNs removed) was performed in 493 patients (stage I, n=225; stage II, n=119; stage III, n=149) at two university hospitals between 2010 and 2016. Cutpoints were as follows: TSR (50%), TILs (median), and TB (Bd0-Bd3). TME features and their association with clinicopathological characteristics, time-to-recurrence (TTR) and overall survival (OS) were analyzed by univariate and multivariate Cox methods.. Results: Among 493 patients, high TSR, low TILs and high TB (Bd1-Bd3) were significantly associated with higher histological grade, larger tumor size, and increased T and N stages. Each of these features was significantly associated with poorer TTR and OS at 5 years. In Cox multivariable analysis, N stage and TSR were the only variables that were significantly associated with TTR and OS (Table). The relative contribution (%) of TSR to TTR ranked second (17.5%) behind N stage (49.2%) and ahead of TILs (7.2%) and TB (0.1%). Conclusions: Among TME features, TSR was the most robust and was significantly and independently associated with TTR and OS. The relative contribution of TSR to TTR was second only to nodal status. [Table: see text]
Glucose Intolerance in Pregnancy and Offspring Obesity in Late Adolescence
Authors: Cole D. Bendor, Aya Bardugo, Ran Shmuel Rotem, Estela Derazne, Hertzel C. Gerstein, Dorit Tzur, Orit Pinhas-Hamiel, Avishai M. Tsur, Tali Cukierman-Yaffe, Yael Lebenthal, Arnon Afek, Gabriel Chodick, Gilad Twig
Journal: Diabetes Care (2022)

Gestational hyperglycemia is associated with deleterious neonatal outcomes, but long-term risks for offspring obesity are less clear. We estimated the odds for offspring adolescent overweight and obesity among mothers with gestational glucose intolerance.In a mother-offspring historical cohort, the Israel military conscription data set was linked to a large health maintenance organization. Included were women who were evaluated at adolescence and underwent two-step gestational diabetes screening (mean age, 31 years) with a 50-g glucose challenge test (GCT), followed by a 100-g oral glucose tolerance test (OGTT) if the result was abnormal. Glucose tolerance categories included gestational normoglycemia, abnormal GCT with normal OGTT, impaired glucose tolerance (IGT; one abnormal OGTT value), and gestational diabetes. The primary outcome was offspring overweight/obesity (BMI ≥85th percentile) at adolescence, measured prior to military conscription. Logistic regression models were applied.Of 33,482 mother-offspring pairs, overweight and obesity were observed in 6,516 offspring. Across increasing categories of pregnancy glycemia, the proportions of offspring with adolescent overweight/obesity increased: normoglycemia, 19%; abnormal GCT with normal OGTT, 22%; gestational IGT, 24%; and gestational diabetes, 25% (P < 0.0001). Corresponding odds ratios after adjustment for the mother's late adolescent characteristics (sociodemographic confounders and BMI) and pregnancy age were 1.2 (95% CI 1.1-1.4), 1.3 (1.2-1.5), and 1.4 (1.3-1.6), respectively. Further adjustment for offspring birth weight percentile and sociodemographic variables did not materially change results. Associations were more pronounced with increasing obesity severity.Gestational glucose intolerance, including categories not meeting the gestational diabetes threshold, was associated with increased odds for offspring overweight/obesity at late adolescence.
PD-L1 score as a prognostic biomarker in Asian patients with early-stage, EGFR-mutated lung cancer.
Authors: Stephanie Saw, Gillianne Lai, Aaron C. Tan, Siqin Zhou, Mei-Kim Ang, Wan-Teck Lim, Ravindran Kanesvaran, Wan Ling Tan, Tanujaa Rajasekaran, Johan Chan, Yi Lin Teh, Boon-Hean Ong, Angela M. Takano, Eng Huat Tan, Sze Huey Tan, Daniel Shao-Weng Tan
Journal: Journal of Clinical Oncology (2022)

8527 Background: Adjuvant Atezolizumab was recently approved in stage II-IIIA non-small cell lung cancer (NSCLC) with PD-L1 ≥1%. However, disease-free survival (DFS) benefit was mainly driven by PD-L1 ≥50% and among EGFR-mutated subgroup, atezolizumab did not demonstrate DFS benefit when PD-L1 0% patients were included. We sought to determine the prognostic value of PD-L1 score in early-stage EGFR-mutated NSCLC. Methods: Consecutive patients with Stage IA-IIIA NSCLC diagnosed 1/1/2010 – 31/12/2019 who underwent curative surgery at National Cancer Centre Singapore with evaluable EGFR and PD-L1 status were included. Co-primary endpoints were 2-year DFS and 5-year overall survival (OS) by Kaplan-Meier method. Results: 455 patients were included (267 EGFR-mutant; 188 EGFR-wildtype). Median age at diagnosis was 65 years, 52.3% (238/455) were males and 62.9% (286/455) were never-smokers. Adenocarcinomas comprised 92.1% (419/455) and 92.5% (421/455) had R0 resection. Stage IA comprised 42.4% (193/455), Stage IB 23.1% (105/455), Stage II 15.8% (72/455) and Stage IIIA 18.7% (85/455). Among EGFR-mutant, 45.3% (121/267) were Ex19del and 41.9% (112/267) were L858R. PD-L1 ≥1% among EGFR-mutant and EGFR-wildtype was 55.8% (149/267) and 60.1% (113/188) respectively (p = 0.361). PDL1 ≥50% was significantly associated with higher stage at diagnosis among EGFR-mutant (p &lt; 0.001) but not EGFR-wildtype (p = 0.319). At median follow up of 47 months, 178 patients had relapsed. Among EGFR-mutant, 2-year DFS comparing PD-L1 0% and PD-L1 ≥1% was 79.0% and 68.9% (p = 0.006) while 5-year OS was 87.6% and 70.6% (p = 0.006) respectively. 2-year DFS and 5-year OS by PD-L1 tertile (as shown in table) revealed that higher PD-L1 score was prognostically worse for both DFS and OS among EGFR-mutant. A similar trend was observed among EGFR-wildtype but did not reach statistical significance, apart from PD-L1 ≥50% which had significantly inferior DFS. Conclusions: Higher PD-L1 score was significantly associated with worse DFS and OS among early-stage EGFR-mutated NSCLC, possibly due to higher stage at diagnosis among PDL1 ≥50%. Our study highlights the poor prognosis of PDL1 ≥50% EGFR-mutated NSCLC in a pre-osimertinib era and underscores the importance of personalised risk-stratified adjuvant strategies. [Table: see text]
Effectiveness of ultrasound-guided obturator nerve interfascial block with an inguinal approach during transurethral resection of bladder tumour: A prospective randomized double-blinded clinical trial
Authors: G. Nohales, R. Rodriguez, M. Corcoy, A. Garcia Larrosa, A. Pardo, I. Andolz, G. Delgado, L. Cecchini
Journal: European Urology (2022)
Hyperestrogenism is associated with sexual function impairment in men – findings from a cross-sectional, real-life study
Authors: L. Boeri, P. Capogrosso, G. Fallara, W. Cazzaniga, L. Candela, F. Belladelli, E. Pozzi, R. Massimiliano, A. Costa, C. Christian, C. Daniele, S. Nicolò, C. Gianmarco, D. Alessia, E. Ventimiglia, R. Matloob, F. Dehò, F. Montorsi, A. Salonia
Journal: European Urology (2022)
MEDB-78. Unified rhombic lip origins of Group 3 and Group 4 medulloblastoma
Authors: Kyle Smith, Laure Bihannic, Brian Gudenas, Qingsong Gao, Parthiv Haldipur, Ran Tao, Igor Iskusnykh, Viktor Chizhikov, Matthew Scoggins, Silu Zhang, Angela Edwards, Mei Deng, Ian Glass, Lynne Overman, Jake Millman, Alexandria Sjoboen, Jennifer Hadley, Kshitij Mankad, Arzu Onar-Thomas, Amar Gajjar, Giles Robinson, Kimberly Aldinger, Volker Hovestadt, Heather Tillman, Brent Orr, Zoltán Patay, Kathleen Millen, Paul Northcott
Journal: Neuro-Oncology (2022)

Abstract Identification and characterization of lineage-specific beginnings of distinct medulloblastoma (MB) subgroups is a fundamental challenge in the field. Genetically engineered mouse models and cross-species transcriptomics have provided mounting evidence of discrete, subgroup-specific developmental origins. Likewise, murine single-cell transcriptional atlases of cerebellar development have recently provided further clues into MB subgroup origins, particularly for poorly defined Group 3 and Group 4-MB. However, initial studies were underpowered to characterize rare populations and lacked robust validation, resulting in incomplete findings. Herein, we leveraged a large harmonized murine cerebellar atlas, targeted lineage enrichment, and integrative multi-omic strategies to deeply dissect MB origins. Isolation of spatially and temporally discrete developmental trajectories of key glutamatergic lineages born out of the murine upper rhombic lip provided an enhanced reference for mapping MB subgroup origins, especially for Group 3 and Group 4-MB. However, human-specific anatomic and cellular complexity, particularly within the rhombic lip germinal zone complicated murine-derived inferences. Further tumor-normal integrations using a novel single-cell atlas of the human fetal cerebellum, companioned with laser-capture micro-dissected transcriptional and epigenetic datasets, reinforced developmental insights extracted from candidate murine cerebellar lineages. Characterization of compartment-specific transcriptional signatures identified in the human upper rhombic lip implicated convergent cellular correlates of Group 3 and Group 4-MB, suggestive of a common developmental trajectory underlying their ancestry. Systematic imaging review and 3D summarization of a large clinical trial series of patient tumors, coupled with our advanced insights into developmental signatures, substantiated subgroup-specific tumor location patterns observed at diagnosis. Together, our results strongly implicate a common lineage trajectory of the upper rhombic lip as the probable origin of Group 3 and Group 4-MB. These important findings provide unprecedented opportunities to explore context-dependent mechanisms of MB pathogenesis and will foster generation of improved preclinical models that more faithfully recapitulate tumor biology.